Pandora: nucleotide-resolution bacterial pan-genomics with reference graphs
Rachel Colquhoun, Michael B. Hall, Leandro Lima, Leah W. Roberts, Kerri M. Malone, Martin Hunt, Brice Letcher, Jane Hawkey, Sophie George, Louise Pankhurst, Zamin Iqbal
Abstract
We present pandora, a novel pan-genome graph structure and algorithms for identifying variants across the full bacterial pan-genome. As much bacterial adaptability hinges on the accessory genome, methods which analyze SNPs in just the core genome have unsatisfactory limitations. Pandora approximates a sequenced genome as a recombinant of references, detects novel variation and pan-genotypes multiple samples. Using a reference graph of 578 Escherichia coli genomes, we compare 20 diverse isolates. Pandora recovers more rare SNPs than single-reference-based tools, is significantly better than picking the closest RefSeq reference, and provides a stable framework for analyzing diverse samples without reference bias.